The purpose of this research program is to investigate renal functional and structural maturation, and the disturbances induced by states of disease. To this end, investigations are planned dealing with (1) various aspects of developmental renal physiology (2) the pathophysiology of renal disease, and (3) the natural history of renal disease, including the influence of various therapeutic agents. Investigations will be made of the physiological changes that take place during the transition from intrauterine to extrauterine life. Glomerulotubular balance in puppies will be studied by characterization PAH transport in puppies. Renal morphometry and interrelationships between glomerular and tubular size will be studied in puppies and guinea pigs, and correlated with functional changes. Studies of renal hemodynamics and the functioning of nephrons at various levels of the cortex will be continued. Adaptation of the immature kidney will be studied in puppies with progressive nephron reduction. The pathophysiology of the respiratory distress syndrome will be studied in animal models. The feasibility of using the neonatal kidney for transplantation will be studied in dogs. The effects of lead poisoning on the kidney will be investigated in experimental and clinical studies. The morphologic and functional development of the congenitally hydronephrotic kidney and the capacity to recover after relief of obstruction will be studied in the lamb and in children with obstructive uropathy. The pathophysiology of renal tubular acidosis will be studied in experimental models in dogs and in studies in children with the proximal and distal forms of disease. The natural history of a number of renal diseases will be studied, including the response to various therapeutic agents. The effect of chronic renal diseases in children on psychosocial as well as biological aspects of growth and development of the patient will be studied.